PROJECT SUMMARY/ABSTRACT: Smoking is an appetitive behavior and stimuli associated with nicotine's desirable effects have been shown to increase smoking urge and behavior. As electronic nicotine delivery systems (ENDS, electronic cigarettes, or e-cigarettes) share salient features of traditional smoking in form and function, it is possible they could generalize as a conditioned cue for smoking urge and behavior. With increasing popularity of e-cigarettes and their recent rapid adoption, exposures to e-cigarette use are increasing as well. Newer tank-based third- generation ENDS ?mods,? modified for user preference and customization, are becoming preferred by vapers for their more powerful delivery, customized vaping experience, and e-liquid variants. ENDS mods have variable-voltage/wattage settings and can be used with e-liquids containing high levels of the primary humectant vegetable glycerin (VG). Both increased power settings and higher VG content can increase vapor production and the throat hit to the user, but this also renders ENDS mods use as more visible which could affect their cue salience. As mods share the least resemblance to traditional cigarettes of all ENDS classes, exposures to their use could be benign or could represent a novel smoking cue. As such, well-controlled, evidence-based research is needed to elucidate whether exposure to mods may affect tobacco use. We propose the first large-scale, controlled study of reactivity to third-generation ENDS mods and their e-liquid constituents in three important and potentially vulnerable subgroups to these exposures in terms of their potential impact on tobacco use and/or smoking relapse: young adult current smokers, persons who converted to vaping from smoking, and former smokers. Study 1 will compare subjective and behavioral responses to a mod cue with high vs. low VG e-liquids, relative to both a non-smoking (water) control cue and a cigarette cue (active comparison) within a diverse sample of young adult daily and nondaily smokers (N=320, 80/cue condition). Study 2 will examine subjective responses to the mods cue with high VG and a cigarette cue within two subgroups that may be particularly vulnerable to relapse to smoking following exposure to e-cigarette cues, i.e., persons who recently converted from smoking to e-cigarettes and former smokers (N=160, 80/subgroup, 40/cue condition). Smoking behavior will not be assessed in Study 2 for ethical reasons as participants are not currently smokers. Moderators (sex, nicotine dependence, ENDS use, etc.) will be conducted to ascertain factors that are associated with sensitivity to the ENDS cue. The results will contribute significantly to scientific knowledge on the effects of ENDS and play a critical role in determining the role of ENDS exposures to factor into the ongoing debate about these devices and their potential benefit versus harm in society. Second-hand exposures to these devices and the salience of their exhaled aerosols (vapor) may be an important part of the equation in evaluating the overall effects of ENDS use in society.